Predicting ligand-binding differences of alpha 1 subtype and alpha 6 subtype of GABA(A) receptor using molecular modeling
文献类型：期刊论文
| 作者 | Ren, Tian-Rui; Ci, Su-Qin; Su, Zhi-Guo |
| 刊名 | JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM
 |
| 出版日期 | 2007-08-20 |
| 卷号 | 816期号:1-3页码:5-11 |
| 关键词 | GABA(A) receptor alpha 1 subtype alpha 6 subtype homology modeling GABA docking study |
| ISSN号 | 0166-1280 |
| 其他题名 | Theochem-J. Mol. Struct. |
| 中文摘要 | The GABA(A) receptors are pentameric combinations of seven subunit families and 16 subunit subtypes. The pharmacological and physiological properties of GABAA receptor are largely determined by the compositions of these subunits and subtype. Among the six alpha subtypes, the at and alpha 6 subtypes are the most divergent, conferring different responsiveness to GABA. To investigate the structural mechanisms that were responsible for the different affinity of GABA to two subtypes, the three-dimensional structure models of the extracellular domain of subtypel and subtype6 were constructed based on the crystal structure of acetylcholine-binding protein. Docking studies were further utilized to find out the differences of ligand-binding pocket that underlie the different pharmacological properties between alpha 6 subtype and alpha 1 subtype. The results showed Tyr157 in loop B of beta 3 subunit played an important role in the recognition of GABA by subtype I and subtype 6. Additionally, the orientation of phenol moiety of Tyr157 in alpha 6 subtype would result in the formation of the higher number of hydrogen bonds and strong hydrophobic contact, which might be the principal cause of high affinity of GABA to alpha 6 subtype. Moreover, the lower docked energy obtained from docking calculation of alpha 6 subtype was consistent with the low EC50 values in vitro. (C) 2007 Elsevier B.V. All rights reserved. |
| 英文摘要 | The GABA(A) receptors are pentameric combinations of seven subunit families and 16 subunit subtypes. The pharmacological and physiological properties of GABAA receptor are largely determined by the compositions of these subunits and subtype. Among the six alpha subtypes, the at and alpha 6 subtypes are the most divergent, conferring different responsiveness to GABA. To investigate the structural mechanisms that were responsible for the different affinity of GABA to two subtypes, the three-dimensional structure models of the extracellular domain of subtypel and subtype6 were constructed based on the crystal structure of acetylcholine-binding protein. Docking studies were further utilized to find out the differences of ligand-binding pocket that underlie the different pharmacological properties between alpha 6 subtype and alpha 1 subtype. The results showed Tyr157 in loop B of beta 3 subunit played an important role in the recognition of GABA by subtype I and subtype 6. Additionally, the orientation of phenol moiety of Tyr157 in alpha 6 subtype would result in the formation of the higher number of hydrogen bonds and strong hydrophobic contact, which might be the principal cause of high affinity of GABA to alpha 6 subtype. Moreover, the lower docked energy obtained from docking calculation of alpha 6 subtype was consistent with the low EC50 values in vitro. (C) 2007 Elsevier B.V. All rights reserved. |
| WOS标题词 | Science & Technology ; Physical Sciences |
| 类目[WOS] | Chemistry, Physical |
| 研究领域[WOS] | Chemistry |
| 关键词[WOS] | AGONIST-BINDING ; A RECEPTORS ; PROTEIN ; SUBUNIT ; DOMAINS ; IDENTIFICATION ; ENVIRONMENT ; RESIDUES ; SUBTYPES |
| 收录类别 | SCI |
| 原文出处 | |
| 语种 | 英语 |
| WOS记录号 | WOS:000248868600002 |
| 公开日期 | 2013-10-15 |
| 版本 | 出版稿 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/3422]  |
| 专题 | 过程工程研究所_研究所（批量导入） |
| 作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100080, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ren, Tian-Rui,Ci, Su-Qin,Su, Zhi-Guo. Predicting ligand-binding differences of alpha 1 subtype and alpha 6 subtype of GABA(A) receptor using molecular modeling[J]. JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM,2007,816(1-3):5-11. |
| APA | Ren, Tian-Rui,Ci, Su-Qin,&Su, Zhi-Guo.(2007).Predicting ligand-binding differences of alpha 1 subtype and alpha 6 subtype of GABA(A) receptor using molecular modeling.JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM,816(1-3),5-11. |
| MLA | Ren, Tian-Rui,et al."Predicting ligand-binding differences of alpha 1 subtype and alpha 6 subtype of GABA(A) receptor using molecular modeling".JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM 816.1-3(2007):5-11. |
入库方式： OAI收割
来源：过程工程研究所
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